Ductal carcinoma in situ (DCIS) transition to invasive tumor is an important issue for breast cancer. The human MCF10DCIS.com cell line (abbreviated as MCF10DCIS) is derived from the human MCF10A breast epithelial cell line. The MCF10DCIS xenografts are similar to human high grade comedo DCIS. In the xenograft assay, MCF10DCIS cells form DCIS-like lesion, remain as DCIS-like lesion in the first few weeks, and then progress into invasive carcinoma. Thus, it is an excellent model to study human breast cancer transition from DCIS to invasive carcinoma. To the best of our knowledge, it is also the only cell model for DCIS transition to invasive carcinoma. We investigated the role of CD44 in breast cancer transition from DCIS to invasive carcinoma by knockdown the expression of CD44 in the MCF10DCIS xenograft model. Our results show that knockdown of CD44 expression in the MCF10DCIS cells enhances DCIS transition to invasive carcinoma. Accordingly, a previous study has shown that CD44 expression is lower in invasive human breast tumors compared with DCIS, especially in luminal A subtype. We have also observed that CD44 expression is lower in the invasive carcinomas compared with DCIS. Furthermore, we provide evidence that CD44 plays a role in maintaining the integrity of the myoepithelial layer. Our study uncovered an unexpected role of CD44 in the prevention of DCIS transition to invasive carcinoma. Our findings have important implications for breast cancer.
Date:
2019-07
Relation:
Cancer Research. 2019 Jul;79(13, Suppl.):Abstract number 1073.